Serotonin in the pathophysiology and treatment of CNS disorders

Abstract

Decades ago, in the 1950s, serotonin (5-hydroxytryptamine, 5-Ht) was discovered in the mammalian central and peripheral nervous systems, and successively, its role as an essential neurotransmitter was revealed. advances in understanding the effect of 5-Ht have represented one of the success stories of neuropharmacology. Since its discovery, an enormous amount of experimental evidence has revealed the pivotal role of this biogenic amine in a bewildering diversity of behavioural and physiological processes. this is not surprising, considering the large distribution of 5-Ht-containing axon terminals throughout the central nervous systems (CNS), although these monoamines are synthesized by a small group of neurons within the brain stem. the serotonergic system is one of the most diffusively organized projection systems of the mammalian brain. the majority of the neurons containing 5-Ht generically called the raphe nuclei are located in the brainstem and in some regions of the reticular formation. Recent receptor discoveries have permitted the identification and classification of up to seven families of 5-Ht receptors (5-Ht1–5-Ht7) to date. all 5-Ht receptors belong to the seven transmembrane domain G-proteincoupled receptor (GPCR) superfamily, except for the 5-Ht3 receptor which is a ligand-gated channel. the 5-Ht1 receptor class is comprised of five receptor subtypes (5-Ht1a, 5-Ht1B, 5-Ht1D, 5-Ht1E and 5-Ht1F), which, in humans, share 40–63 % overall sequence identity and couple preferentially, although not exclusively, to Gi/o to inhibit caMP formation. among the multiple classes of 5-Ht receptors described in the CNS, much attention has been devoted to the 5-Ht2 receptor family since it has been shown by experimental and clinical observation to represent a possible therapeutic this special issue is in honour of Ennio Esposito, who devoted his unfortunately short but productive scientific career to serotonin research and made significant contributions to the field of neuropharmacology of monoaminergic systems in neuropsychiatric disorders. after receiving his degree in Medicine at the University of Chieti, Ennio moved to Milan to the laboratory of Neuropharmacology at the Institute of Pharmacological Research Mario Negri, under the supervision of Rosario Samanin. Successively, Ennio did his postdoc in the USa. at the Department of Psychiatry and Pharmacology at Yale University School of Medicine, New Haven, in the laboratory of Dr. Benjamin S. Bunney. Back in Italy, in 1989, he joined the Consorzio Mario Negri Sud, a Biomedical and Pharmacological Research Centre at Santa Maria Imbaro, Chieti. In this new institution, a few miles from his hometown, he created and directed the laboratory of Neurophysiology for about 20 years. the aim of this special issue is to present recent developments in research areas Ennio has been particularly involved in, that is, the serotonin receptors, especially the 5-Ht2C subtype. It includes 18 papers written by several of his former students, co-workers and friends, as well as by distinguished international researchers with similar research interests.